Understanding the biology of uveal melanoma to develop novel therapeutics. Mentor: Mathieu Bakhoum
Pathology and Molecular Medicine Students and their Research
Developing systems for skin modelling using 3D bioprinting and engineering biomaterials for such applications”.
Mentor: Themis Kyriakides
Cancer immunology and clinical toxicology with a focus on how the tumor microenvironment and epigenetic modifications influence immune system dynamics, leading to drug resistance and metastatic progression. Using both murine and patient-derived ex vivo tumors to generate 3D organoid cultures, I investigate genetic drivers of immune suppression. By integrating pharmacological and genomic approaches, we hope to determine mechanisms of resistance in cancer therapy, and biomarkers for clinical prognosis.
Mentor: Marcus Bosenberg
Seeking to understand and recapitulate the features of endocrine cellular differentiation to develop cell-based therapeutics. Mentors: Diane Krause and Zachary Smith.
Investigating the roles of antitumor CD4+ T-cells in lung cancer.
Mentor: Kurt Schalper
Exploring alterations in tumor suppressor genes that promote tumor growth in EGFR-driven lung adenocarcinomas and elucidating potential therapeutically targetable pro-tumorigenic pathways.
Mentor: Katerina Politi
Identifying synthetic lethal drug interactions in brain cancer for the development of novel therapeutics.
Mentor: Ranjit Bindra
"Investigating the potential leukemogenic role of the RNA-binding motif protein 15 (RBM15) when it is aberrantly fused with the megakaryoblastic leukemia 1 (MKL1) protein through in vitro and in vivo models of acute megakaryoblastic leukemia (AMKL) – thereby contributing to defining novel strategies in regulating hematopoiesis and treating leukemia.”
Mentor: Diane Krause
Characterizing the role of m6A RNA modification in hematopoietic stem cell development and innate immune signaling.
Mentor: Stephanie Halene
Leveraging functional genomic approaches in genetically engineered mouse models (GEMMs), patient derived xenografts (PDXs), and cell lines to identify transcriptional and epigenetic mechanisms that promote tumor plasticity. Specifically, I am utilizing these approaches to unlock novel therapeutic strategies in small cell lung cancer (SCLC).
Mentor: Arnaud Augert
Understanding the immunomodulatory role and clinical significance of cancer cell HLA class-II expression in human lung carcinomas. Mentor: Kurt Schalper.
Studying mechanisms of acquired resistance to KRAS-targeting therapies based on pharmacologic and genetic vulnerabilities using drug and CRISPR screens in KRAS knockout pancreatic cancer cells and dissecting KRAS signaling network via optogenetic tools.
Mentor: Mandar Muzumdar
Aging-associated changes (mRNA, protein and epigenetic DNA methylation) in liver hepatocyte populations during homeostatic and damage conditions.
Mentors: Albert Higgins-Chen
Investigating the roles and interactions between BAP1 and PRC1 in driving the progression of uveal melanoma from the GEP1 phenotype to the aggressive, metastatic GEP2 phenotype and exploring potential therapeutic targets to prevent the GEP2 transition.
Mentor: Mathieu Bakhoum
Characterizing resistance mechanisms for antibody-drug conjugates (ADCs) and designing diagnostic assays for ADC treatments: ADCs are a novel class of cancer therapy that links antibody specificity to potent cytotoxic molecules. Although showed significant improvement in clinical trials, ADCs still exhibit resistance and toxicities. Hence, I aim to investigate the resistance mechanisms for ADCs, identify predictive biomarkers for ADC responders, and design standardized and clinically applicable diagnostic assays for screening.
Mentor: David Rimm
Understanding the immunobiology of human solid tumors and exploring the mechanism or potential approaches to increase the proportion of cancer patients responding to cancer immunotherapy. Mentor: Kurt Schalper.
The relationship between the gene TSP2 and diseases, and TSP2-related biomaterials.
Mentor: Themis Kyriakides
"Towards overcoming therapeutic resistance in brain metastatic NSCLC: Central nervous system (CNS) metastasis is frequently observed in EGFR-mutant non-small cell lung cancer (NSCLC) accompanied by the development of lesions resistant to Osimertinib. We are focusing on the contributions of the tumor microenvironment and extracellular matrix to the persistence of metastatic-resistant NSCLC clones."
Mentor: Don Nguyen
Characterization of cerebrospinal fluid factors influencing leptomeningeal metastases.
Mentor: Don Nguyen
Investigating therapeutic vulnerabilities to NAD+ depletion for pediatric solid tumors.
Mentors: Ranjit Bindra and Juan C. Vasquez
Leveraging epigenetic targets to elucidate mechanisms of brain metastasis: Caro is interested in identifying novel mechanisms via which epigenetic regulators control the metastasis of lung adenocarcinomas.
Mentor: Don Nguyen
AMKL is a rare leukemia characterized by the improper development of megakaryocytes. In neonates, AMKL is most often caused by a genetic translocation resulting in the RBM15-MKL1 fusion protein. Madeline's work focuses on the effect of this fusion protein on normal and malignant hematopoiesis with the goal of elucidating the mechanism by which it promotes leukemogenesis.
Mentor: Diane Krause
Exploring chromatin biology and epigenetic regulatory mechanisms in small cell lung cancer (SCLC). Mentor: Arnaud Augert.
Investigating the epigenetic mechanisms of reprogramming and aging in fibroblasts.
Mentor: Albert Higgins-Chen
Next-generation diagnostic approaches for HER2-low breast cancer and trastuzumab deruxtecan therapy: The current immunohistochemical (IHC) assays for determining HER2-low status are no better than a coinflip (due to an estimated 75% discordance rate amongst pathologists scoring 0 vs. 1+/2+). These legacy assays for HER2 were designed over 20 years ago to detect amplified HER2 cases, and are now are being wrongly applied to select patients for emerging HER2-low therapies (e.g. trastuzumab deruxtecan). In the Rimm lab, we have developed a solution: a high-sensitivity HER2 assay that is designed to quantify unamplified, low HER2 expression rather than rely on subjective semi-quantitative scoring by pathologists using legacy IHC assays. We plan to carefully evaluate the HS-HER2 assay and it's predictive value towards T-DXd response to in comparison to the legacy IHC assays. We expect that our results will encourage adoption of high-sensitivity, analytic assays for HER2 expression that oncologists can use to be certain their patients are receiving the best treatment option available. My research will also include investigating the biology of HER2-low breast cancer and the molecular mechanisms outside of HER2 expression associated with T-DXd antibody-drug conjugate response.
Mentor: David Rimm
Exploring mechanisms of therapy resistance in EGFR-driven non-small cell lung cancer (NSCLC): This project aims to characterize off-target mechanisms that contribute to therapy resistance and identify exploitable vulnerabilities to resensitize NSCLC tumors to therapy.
Mentor: Katerina Politi
Applying high-throughput genomic technologies to characterize MHC class II antigen processing/presentation and to identify new T cell targets in patient tumors. Ultimately we aim to explore new strategies to leverage T cell receptor-based therapies that enhance intrinsic antitumor immune responses in cancer patients.
Mentor: Mark Lee
Investigations in telomere maintenance and regulation by Pot1b. To explore the role of Pot1b in telomere length maintenance during telomerase-mediated telomere elongation and alternative lengthening of telomeres.
Mentor: Sandy Chang
My project involves the investigation of the role of extracellular vesicles in inflammation, tissue remodeling and repair. Via genetic and synthetic biology approaches, I aim to decipher the role they play in these processes and exploit them for the development of novel constructs consisting of hydrogels, extracellular vesicles, and drugs. Such constructs will be employed in regenerative medicine applications and the treatment of chronic wounds.
Mentor: Themis Kyriakides
Researching the role of RNA splicing in pancreatic cancer with the goal of identifying novel therapeutic targets that can improve both the quality of life and survival of patients.
Mentor: Luisa Escobar-Hoyes